This study determined the contribution of chronic salt loading and early loss of ovarian hormones on diastolic function in the hypertensive female mRen(2). Lewis rat, a monogenetic strain that expresses the mouse renin-2 gene in various tissues. Estrogen-intact mRen2 rats fed a high salt (HS) (8% sodium chloride) diet exhibited early diastolic dysfunction when compared to normal salt-fed (NS) (1% sodium chloride) rats. In contrast, ovariectomized (OVX) rats on either NS or HS diets showed impaired relaxation with evidence of elevated left ventricular filling pressures (E/e') or pseudonormalization. This more advanced stage of diastolic dysfunction was associated with increases in interstitial cardiac fibrosis and high circulating levels of aldosterone, two factors leading to reduced ventricular compliance. These findings may explain the preponderance of diastolic dysfunction and diastolic heart failure in postmenopausal women and provide a potential animal model for evaluating prevention and treatment interventions for this disorder.